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OBJECTIVE: The aim of this study was to compare the use of semi-automated (Medax Velox 2; Poggio Rusco, Italy) and automated (Bard Magnum Biopsy Instrument; Covington, GA, USA) core biopsy needles, for ultrasound guided breast biopsy. MATERIALS AND METHODS: A 14G semi-automatic spring loaded core biopsy needle with a 22-mm-throw (Medax Velox 2; Poggio Rusco, Italy) and 14-gauge automated needle device with a 22-mm-throw biopsy gun (Bard-Magnum Biopsy Instrument, Covington, GA, USA) were used for breast biopsies under ultrasound guidance on alternate months during the study period between July 2009 and May 2011. One hundred and sixty lesions were biopsied and specimens were sent for histological evaluation. RESULTS: The automated needle obtained a higher number of histology reports at 84% (67/80) as compared with the semiautomated needle at 60% (48/80) (Fisher exact test, p value=0.023). Inadequate samples with the automated needle were much less at 9% (7/60) than with the semiautomated needle at 23% (18/60) (Fisher exact test, p value=0.028). The semi-automated needle showed slightly less fragmented samples. However, the number of fragmented samples with definitive diagnosis was slightly higher with the automated compared with the semiautomated needle, at 16% (13/80) and 13% (10/80) respectively. Compared with histology of 29 lesions that were excised, the semi-automated needle had higher sensitivity (100%) but lower specificity (75%) and accuracy (90%) compared with the automated needle (88% sensitivity, 100% specificity, 95% accuracy). CONCLUSION: Definitive diagnosis from the study samples slightly favours the use of automated core biopsy needle as compared to semi-automated core biopsy needle.
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Beta-adrenergic receptor (ßAR) inotropic effects are attenuated and muscarinic receptor-mediated inhibition thereof is enhanced in heart failure. We investigated if increased G(i) activity contributes to attenuated ßAR-inotropic effects and potentiates muscarinic accentuated antagonism in failing rat ventricle. Contractility was measured in ventricular strips and adenylyl cyclase (AC) activity in ventricular membranes from rats with post-infarction heart failure (HF) or Sham-operated controls (Sham). The maximal ßAR-mediated inotropic effect of isoproterenol was reduced by ~70% and basal, ßAR- & forskolin-stimulated AC activity was significantly lower in HF vs. Sham. Carbachol-evoked antagonism of the ßAR-mediated inotropic response was complete only in HF despite a ~40% reduction in the ability of carbachol to inhibit ßAR-stimulated AC. However, neither the relative efficacy (contractility decreased by ~46%) nor the potency of carbachol to inhibit the ßAR inotropic response differed between Sham and HF ventricle. Pertussis toxin (PTX) inactivation of G(i) did not increase the maximal ßAR inotropic effect or the attenuated basal, ßAR- & forskolin-stimulated AC activity in HF, but increased the potency of isoproterenol only in Sham (~0.5 log unit). In HF ventricle pretreated with PTX, simultaneous inhibition of phosphodiesterases 3,4 (PDE3,4) alone produced a larger inotropic response than isoproterenol in ventricle untreated with PTX (84% and 48% above basal respectively). In the absence of PTX, PDE3,4 inhibition evoked negligible inotropic effects in HF. These data are not consistent with the hypothesis that increased G(i) activity contributes to the reduced ßAR-mediated inotropic response and AC activity in failing ventricle. The data, however, support the hypothesis that G(i), through chronic receptor independent inhibition of AC, together with PDE3,4 activity, is necessary to maintain a low basal level of contractility.
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Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Insuficiencia Cardíaca/metabolismo , Ventrículos Cardíacos/fisiopatología , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/metabolismo , Adenilil Ciclasas/metabolismo , Agonistas Adrenérgicos beta/farmacología , Animales , Carbacol/farmacología , Cardiotónicos/farmacología , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/antagonistas & inhibidores , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/metabolismo , Técnicas In Vitro , Isoproterenol/farmacología , Masculino , Agonistas Muscarínicos/farmacología , Infarto del Miocardio/fisiopatología , Toxina del Pertussis/farmacología , Inhibidores de Fosfodiesterasa 3/farmacología , Inhibidores de Fosfodiesterasa 4/farmacología , Quinolonas/farmacología , Ratas , Ratas Wistar , Rolipram/farmacología , Presión VentricularRESUMEN
BACKGROUND AND PURPOSE: ß-Adrenoceptor (ß-AR)-mediated inotropic effects are attenuated and G(i) proteins are up-regulated in heart failure (HF). Muscarinic receptors constitutively inhibit cAMP formation in normal rat cardiomyocytes. We determined whether constitutive activity of muscarinic receptors to inhibit adenylyl cyclase (AC) increases in HF and if so, whether it modifies the reduced ß-AR- or emergent 5-HT4-mediated cAMP-dependent inotropic effects. EXPERIMENTAL APPROACH: Contractility and AC activity were measured and related to each other in rat ventricle with post-infarction HF and sham-operated (Sham) controls with or without blockade of muscarinic receptors by atropine and inactivation of G(i) protein by pertussis toxin (PTX). KEY RESULTS: Isoprenaline-mediated inotropic effects were attenuated and basal, isoprenaline- and forskolin-stimulated AC activity was reduced in HF compared with Sham. Atropine or PTX pretreatment increased forskolin-stimulated AC activity in HF hearts. ß-AR-stimulated AC and maximal inotropic response were unaffected by atropine in Sham and HF. In HF, the potency of serotonin (5-HT) to evoke an inotropic response was increased in the presence of atropine with no change in the maximal inotropic response. Interestingly, PTX pretreatment reduced the potency of 5-HT to evoke inotropic responses while increasing the maximal inotropic response. CONCLUSIONS AND IMPLICATIONS: Although muscarinic constitutive inhibition of AC is increased in HF, it does not contribute to the reduced ß-AR-mediated inotropic effects in rat ventricle in HF. The data support the hypothesis that there are differences in the functional compartmentation of 5-HT4 and ß-AR AC signalling in myocardium during HF.
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Adenilil Ciclasas/metabolismo , Cardiotónicos/farmacología , AMP Cíclico/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/antagonistas & inhibidores , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/efectos de los fármacos , Receptores Muscarínicos/metabolismo , Inhibidores de Adenilato Ciclasa , Agonistas Adrenérgicos beta/farmacología , Animales , Cardiotónicos/agonistas , AMP Cíclico/agonistas , Insuficiencia Cardíaca/metabolismo , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/fisiopatología , Técnicas In Vitro , Masculino , Antagonistas Muscarínicos/farmacología , Contracción Miocárdica/efectos de los fármacos , Músculos Papilares/efectos de los fármacos , Músculos Papilares/metabolismo , Músculos Papilares/fisiopatología , Ratas , Ratas Wistar , Receptores Adrenérgicos beta/metabolismo , Receptores de Serotonina 5-HT4/metabolismo , Agonistas del Receptor de Serotonina 5-HT4/farmacología , Antagonistas de la Serotonina/farmacologíaRESUMEN
BACKGROUND AND PURPOSE: Muscarinic stimulation increases myofilament Ca(2+) sensitivity with no apparent inotropic response in normal rat myocardium. Increased myofilament Ca(2+) sensitivity is a molecular mechanism promoting increased contractility in failing cardiac tissue. Thus, muscarinic receptor activation could elicit inotropic responses in ventricular myocardium from rats with heart failure, through increasing phosphorylation of myosin light chain (MLC). EXPERIMENTAL APPROACH: Contractile force was measured in left ventricular papillary muscles from male Wistar rats, 6 weeks after left coronary artery ligation or sham surgery. Muscles were also frozen, and MLC-2 phosphorylation level was quantified. KEY RESULTS: Carbachol (10 micromol.L(-1)) evoked a positive inotropic response only in muscles from rats with heart failure approximating 36% of that elicited by 1 micromol.L(-1) isoproterenol (20 +/- 1.5% and 56 +/- 6.1% above basal respectively). Carbachol-evoked inotropic responses did not correlate with infarction size but did correlate with increased left ventricular end diastolic pressure, heart weight/body weight ratio and lung weight, primary indicators of the severity of heart failure. Only muscarinic receptor antagonists selective for M(2) receptors antagonized carbachol-mediated inotropic effects with the expected potency. Carbachol-evoked inotropic responses and increase in phosphorylated MLC-2 were attenuated by MLC kinase (ML-9) and Rho-kinase inhibition (Y-27632), and inotropic responses were abolished by Pertussis toxin pretreatment. CONCLUSION AND IMPLICATIONS: In failing ventricular muscle, muscarinic receptor activation, most likely via M(2) receptors, provides inotropic support by increasing MLC phosphorylation and consequently, myofilament Ca(2+) sensitivity. Enhancement of myofilament Ca(2+) sensitivity, representing a less energy-demanding mechanism of inotropic support may be particularly advantageous in failing hearts.
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Miosinas Cardíacas/metabolismo , Insuficiencia Cardíaca/metabolismo , Ventrículos Cardíacos/metabolismo , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/metabolismo , Cadenas Ligeras de Miosina/metabolismo , Músculos Papilares/metabolismo , Receptores Muscarínicos/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Calcio/metabolismo , Carbacol/farmacología , Cardiotónicos/farmacología , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/efectos de los fármacos , Técnicas In Vitro , Isoproterenol/farmacología , Masculino , Contracción Miocárdica/fisiología , Infarto del Miocardio/fisiopatología , Músculos Papilares/efectos de los fármacos , Fosforilación , Unión Proteica , Ratas , Ratas WistarRESUMEN
OBJECTIVES: To assess the prevalence of four categories (domains) of menopausal symptoms as markers for quality of life in nine ethnic groups of Asian women. To evaluate changes in quality of life (MENQOL scores) in Asian women following hormone therapy. METHODS: A prospective, randomized, double-blind, multinational clinical trial in 1028 healthy postmenopausal women of nine ethnic groups from 11 Asian countries/regions. Following 2 weeks of baseline observation, the women received one of three conjugated estrogens (CE)/medroxyprogesterone acetate (MPA) doses (in mg) daily for 24 weeks: 0.625/2.5, 0.45/1.5, or 0.3/1.5. At baseline and at the end of weeks 4, 12 and 24 following the start of therapy, the study participants were asked to record, on a menopause-specific quality of life (MENQOL) questionnaire, 29 menopausal symptoms, as experienced during the preceding month. The symptoms were categorized into four domains: vasomotor, psychosocial, physical and sexual. RESULTS: The baseline (pretreatment) symptom scores in each of the four domains varied substantially among the different ethnic groups, ranging from 2.21 to 5.71 in the vasomotor, 2.37-5.96 in the psychosocial, 2.66-5.39 in the physical, and 2.11-6.55 in the sexual domain. Overall, Vietnamese and Pakistani women had the highest baseline scores, i.e. were most afflicted by each set of symptoms in a given domain, and Indonesian, Malay, Taiwanese and Thai women were least afflicted. In the overall population, intervention resulted in statistically significant decreases in the scores of all four domains within 4 weeks of intervention. The beneficial effects were similar in the three dose groups. CONCLUSIONS: The prevalence of four domains of menopausal symptoms, representative of quality of life as recorded on a MENQOL questionnaire, varies considerably among ethnic groups of Asian women. The MENQOL scores in the overall population were significantly lowered in the course of the study, indicating an improvement in quality of life. In the absence of a placebo group, the relative contribution of hormones and placebo in our intervention is unknown.